THORACIC ACTINOMYCOSISIn 1949 Suteev treated 12 patients byimmunization with " actino-filtrate" and...

Thorax (1957), 12, 99.

THORACIC ACTINOMYCOSISBY

MICHAEL BATES AND GORDON CRUICKSHANKFrom the North Middlesex Hospital and the Leicester Chest Unit

(RECEIVED FOR PUBLICATION JANUARY 9, 1957)

Thoracic actinomycosis was first described byPonfick in 1882. It has been a serious disease, and,until recent years, there has been no satisfactorytreatment. The literature is extensive and variousforms of therapy have been claimed as successful,but the failures have been more impressive. Themortality rates quoted by different authors havevaried from 75% to 100%; but since 1940 theresults of treatment have improved. It is nowreasonable to expect a 90% cure rate for all casesof thoracic actinomycosis, provided that antibiotictreatment is given in sufficient quantity and foran adequate length of time. There has beenuncertainty both in the nomenclature of the causa-tive organism and also in the aetiology and classi-fication of the thoracic manifestations in man. Itis because of this radical change in treatment andimprovement in the mortality rate that we nowreview the subject.

HISTORICAL SURVEYBollinger (1877) first used the term " actinomyco-

sis" with reference to a disease of cattle in whichthere was a woody swelling of the tongue anddiffuse enlargement of the jaw. In the same yearHarz (1877) suggested the use of the term " rayfungus" or Actinomyces bovis for the delicate,branching mycelial filaments which caused thedisease in cattle. Israel (1878, 1879) was the firstto find the organism in human necropsy materialand in 1887 gave a clinical description. Bostroem(1890) described an aerobic form of the organismin cattle and in man; this form was not acid-fastand subsequently became known as Actinomycesgraminis. Acland reported the first case of humanactinomycosis in this country in 1884 (quoted byFoulerton, 1913). Hodenpyl (1890) wrote the firstreport from America of two fatal cases of thoracicactinomycosis. Bostroem (1890) gave the firstbacteriological description of the organism, whilein the same year Wolff and Israel (1891) wrote adescription of the pathology based upon twohuman cases; they isolated an anaerobic form

which grew at body temperature, and showed truebranching. Nocard (1888) described the pathogenicaerobic genus which was subsequently calledNocardia. Eppinger (1890) isolated a furtheraerobic form which was acid-fast called Actinomycesasteroides from a human brain abscess, and thistype is also occasionally found in lung infections.In 1905 Wright established the term Actinomycesbovis for the anaerobic form, and this nomenclaturecontinued until 1949 when the Medical ResearchCouncil (memorandum No. 23, 1949) decided thatthe anaerobic organism responsible for all humaninfections should subsequently be known asActinomyces israeli.

REVIEW OF THE LITERATURE

Before 1940 thoracic actinomycosis was treatedby various methods; occasionally one of thesewas used alone but more often in conjunction withother types of treatment. We have reviewed theliterature on this subject under the different typesof therapy used rather than in their chronologicalorder of trial. The majority of papers concern asmall number of cases, and there are few articlesin which a significant number have been treatedby any one method.

Trevithick (1906) reported an interesting case ofactinomycotic lung abscess which was expectorated,and resolved spontaneously without treatment.A year later this patient developed abdominalactinomycosis which was cured by iodine and radio-therapy. At the beginning of a long list of specifictherapeutic measures this case report serves toremind us of the body's natural resistance to thedisease provided it is given some help in the wayof general supportive measures. Vinson andSutherland (1926) also mention a case where aresistance to the disease had been acquired. In1897 their patient developed an actinomycoticulcer of the tibia and not until 1924 did the diseasemanifest itself again by the development of anoesophago-bronchial fistula.

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MICHAEL BATES and GORDON CRUICKSHANK

TREATMENT

VACCINESWynn (1908) reported a case ofthoraco-abdominal

actinomycosis successfully treated with a vaccine.Neuber (1940) also claimed satisfactory resultsfrom vaccine therapy in cervical and pulmonaryactinomycotic infections. In 1949 Suteev treated12 patients by immunization with " actino-filtrate"and seven were apparently cured, including onepulmonary case.

IODINE IN VARIOUS FORMSFor many years it was thought that iodine had

a specific action upon the Actinomyces israeli; butit is now realized that the benefit gained fromiodine therapy is the result of resorption of fibroustissue, which is always abundant in any actino-mycotic lesion, thus allowing other agents such asthe sulphonamides or penicillin to get into imme-diate contact with the causative organism. Fouler-ton (1913) reported a pleuropulmonary infectionpresenting as a breast abscess and finally healingafter treatment with large doses of potassiumiodide for a year. Preston (1928) reported twocases of actinomycotic lung abscess and severebronchitis which showed marked improvement oniodides by mouth in conjunction with 20 ml. of" lipiodol" injected into the trachea. Anothercase in which endotracheal iodine was consideredto be of importance was reported by McHardyand Browne (1943). Their patient had an actino-mycotic granuloma obstructing the middle lobebronchus and was treated wlth 300 grains ofpotassium iodide daily for 80 days in conjunctionwith two bronchograms.

RADIOTHERAPY AND RADIUM IMPLANTSHarsha, of Chicago (1904), first treated a case of

actinomycosis with radiotherapy, and this form oftreatment was later popularized by Heyerdahl in1914. Cope (1915) described a case with multiplechest-wall sinuses treated by radium implantations.Desjardins (1928) reported a pulmonary case curedby a large dosage of radiotherapy, and Smith(1934) similarly treated 21 pulmonary cases, result-ing in the cure of two, the improvement of twoothers, and the death of the remainder. Heconsidered that the exact action of the x raysupon the actinomyces in vivo was not known, andthat as large a dose as possible should be givenwithout causing permanent damage to the skin.Stewart-Harrison (1934) demonstrated the efficacyof radiotherapy for cervical infections by curing

20 cases; but in eight cases of abdominal andpulmonary disease it had no effect and all thepatients died. Williams (1944) considered radio-therapy to be the most useful therapeutic agent andreported two thoracic cases so treated, one ofwhich was cured.

THYMOLMyers (1937) reported five cases of actinomycosis

treated with 10% thymol, two of them being thoraciccases; one of these died and the other was aliveand well a year later. Etter and Schumacher (1939)also claimed a satisfactory response in treating acase with 0.65 g. of thymol by mouth daily for17 days.

SURGICAL DRAINAGE AND EXCISIONThere are few reports of cases trnated by surgery

alone, most having been treated by surgery inconjunction with other forms of therapy. The twotypes of thoracic disease most likely to respond tosurgical drainage alone are the chest wall abscesswithout underlying pleuropulmonary infection, andthe pleural empyema. Excision of the lung, bylobectomy or pneumonectomy, has only provedsuccessful in conjunction with sulphonamide orpenicillin therapy.

Cutler and Gross (1940) considered surgery theonly treatment likely to be successful in thiscondition, and mention a mortality rate of over95% for all other methods of treatment.

SURGERY IN CONJUNCTION WITH VACCINE, IODINE,THYMOL, OR RADIOTHERAPY

Colebrook (1921) advocated surgery in conjunc-tion with vaccine in doses of 4 to 10 million frag-ments. Six thoracic cases so treated all died.Bigland and Sergeant (1923) reported a case ofactinomycotic empyema and staphylococcal peri-carditis satisfactorily treated by rib resection inconjunction with collosol iodine injected intra-venously and into the pleural and pericardial sacstogether with potassium iodide by mouth. Torek(1926) produced improvement in a case with mul-tiple chest wall abscesses and a bronchocutaneousfistula by incision in conjunction with large dosesof potassium iodide. Harris and Priestley (1944)reported a fatal case originating in the skin withmiliary pulmonary lesions which showed noresponse to iodides, thymol, and radiotherapy.Benbow, Smith, and Grimson (1944) collected 26thoracic cases from the literature, 25 of whichwere dead at that time. They also reported twocases of infection with Nocardia asteroides which

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were well a year after treatment with sulphonamides,radiotherapy, iodides, and surgery. A case ofactinomycotic empyema and pulmonary infectionwas reported by Jacob (1944) as being cured byiodides in conjunction with open drainage. Sixothers reported by Kolouch and Peltier (1946),which were treated by surgery, iodides, and irradia-tion, all died. Wangensteen (1932) reported a casewith extensive involvement of the lung and chestwall treated satisfactorily by repeated surgery andiodides, until the patient eventually died of acerebral abscess. He also treated six other casesof severe thoracic infection by radical surgery,iodides, and radiotherapy, all of which died (1936).Good (1934) reported a case to be improved byradical excision and thoracoplasty associated with600 grains of potassium iodide daily.Cope (1938) in his monograph on actinomycosis

gave a full summary of the various treatmentsused. He mentioned Chitty's method of givingtincture of iodine in milk, injection of normallymph node extracts, and " actinomycine," avaccine used by several Argentine workers. Copealso reported satisfactory healing in a case treatedwith vaccine and diathermy excision. In 1939Cope advocated surgery for the opening up ofsinuses only, and did not advise the excision oflarge infiltrating areas.Two thoracic cases were well two years after

radical surgery, massive iodides, and radiotherapygiven by Bisgard (1939). Davis (1941) reported46 cases of all types of actinomycosis and consideredthat Lugol's wet dressings, iodides to the limit oftolerance, radiotherapy, and surgery combinedwere the best forms of treatment.

SULPHONAMIDESSince 1940 the treatment of thoracic actinomycosis

has been revolutionized by the introduction first ofthe sulphonamides and later of penicillin. Thevarious forms of sulphonamides have all had theirindividual successes, and where one type has faileda good result has been obtained by using anothertype or a combination of sulphonamides.Morton (1940) was the first to report improvement

in a case of pulmonary actinomycosis treated withsulphonamides. Dobson, 1-folman, and Cutting(1941) and Wilkinson (1941) were also among thefirst to report satisfactory results with sulphon-amides. Mitchell (1942) reported a thoraco-abdominal case which had failed to respond tovaccines and iodides but was apparently curednine months after a course of a sulphapyridine.Lidbeck (1942) reported a fatal case from metastaticspread, in which sulphanilamide, sulphapyridine,

I

and sulphathiazole had been given continuouslyfor 14 months without producing any toxic effects.A dramatic cure with sulphadiazine was claimedby Ladd and Bill (1943). Lyons, Owen, and Ayers(1943) report two cases, one being well two yearsafter treatment with iodides, surgery, sulphathiazole,and sulphanilamide, the other being improvedafter five months' treatment with sulphadiazine.Watkins (1944) reported two children aged 3 yearsand 18 months respectively suffering from actino-mycotic empyemata who were treated successfullyby drainage and sulphonamides and by aspirationand sulphonamides respectively. Auspaugh (1945)reported a case of miliary spread from which thepatient died in spite of sulphonamides and generalsupportive measures.

PENICILLIN ALONE OR COMBINED WITH OTHERFORMS OF THERAPY

Penicillin has proved a more powerful agent thanthe sulphonamides, and, even if not always successfulby itself, it has been used to good effect in con-junction with surgery and occasionally sulphon-amides.

In 1943 Florey and Florey reported the first twocases of thoracic actinomycosis treated by smalldoses given four-hourly through a duodenal tubewithout having any effect on the course of thedisease; the other was a pleuropulmonary casewhich was well four months after drainage of anempyema and five weeks' penicillin therapy.

Keeney, Ajello, and Lankford (1944) carried outin vitro experiments with the sulphonamides andpenicillin, and found that sulphamezathine, sulpha-diazine and sulphathiazole were more effectiveagainst Actinomyces bovis than sulphanilamide;they also showed that Actinomyces bovis wasinhibited and apparently killed by a concentrationof 0.01 Oxford units of penicillin per millilitre ofmedium. Shulman (1944) treated a case with a totalof 3 mega units of penicillin in five courses overa period of one year. Considerable temporaryimprovement was noticeable after each shortcourse, but the patient eventually died; this illus-trated the efficacy of the drug but the inadequacyof the dosage. Christie and Garrod (1944) gavea preliminary report on the first clinical penicillintrials in this country and included two thoraciccases both of which are included in this series andoriginally reported by Roberts, Tubbs, and Bates(1945). Walker and Hamilton (1945) reported sixcases, one being of widespread disease with pul-monary involvement which responded dramaticallyto moderate penicillin dosage after a previousfailure to respond to sulphonamide therapy.

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Lynch and Holt (1945) reported a pleuropulmonarycase with pericardial and cardiac involvement whichfailed to respond to iodides, sulphonamides, andradiotherapy. One hundred thousand units ofpenicillin were given during the last 48 hours oflife. Culture of the pleural fluid grew Actinomycesgraminis. Jones and Brownell (1945) reported twocases of thoracic actinomycosis after hysterectomy,both of which responded to penicillin. Dobsonand Cutting (1945) described 16 cases of actino-mycosis, three being pulmonary in origin. Two ofthese cases were greatly improved by sulphonamidesand penicillin, while the third case, in which Nocardiaasteroides was grown from the sputum, died inspite of sulphadiazine therapy.Kay and Meade (1945) reported 93 cases of

actinomycosis, two being pulmonary in type; thelatter were cured by pulmonary resection inassociation with chemotherapy. They came to theconclusion that penicillin was better than thesulphonamides, but that the two combined weremore effective still. A chest wall abscess in a girlaged 10 was cured by local and systemic penicillinfollowed by a two months' course of iodine. Sevenpatients were cured by Poppe (1946), three of whomwere treated by lobectomy and penicillin. Shaw,Holt, and Ray (1946) reported two, one of whomresponded to peniciLlin and sulphadiazine therapy,and the other to empyema drainage and penicillin;in the first of these the infection was due to Nocardiaasteroides. Kay (1946) described two cases of thebronchopulmonary form in which resections wereperformed in conjunction with chemotherapyduring the subacute stage of the disease. Heconsidered segmental resection to be unwise,because the fissures were almost invariably obliter-ated and the danger of causing an extension of thedisease was high. He therefore preferred pneu-monectomy to lobectomy. In 1947 Kay reportedfive more cases; two of these were treated bypneumonectomy and two by lobectomy and all ofthem with penicillin and sulphadiazine. Whilehe considered that penicillin and sulphadiazinewere the most effective therapeutic agents onclinical grounds, preliminary evidence from experi-ments in vitro suggested that streptomycin wasmore effective against the Actinomyces israeli thaneither penicillin or the sulphonamides. Pyper(1947) and Hollis and Hargrove (1947) reportedfurther cases treated by sulphonamides and peni-cillin. Moore (1947) believed that the introductionof chemotherapy permitted more radical surgeryin the acute stage of the disease. Adamson andHagerman (1948) cured an infection of the rightlower lobe with combined penicillin and sulphon-

amide therapy. Nichols and Herrell (1947) reported22 pulmonary cases, nine of which were treatedwith penicillin, five being cured; 13 were not givenpenicillin and of these five were improved and theremainder died. Robinson and Tasker (1949)reported 12 further thoracic cases, and came tothe conclusion that sulphonamide or penicillintherapy had no advantage over the older types oftreatment. Campbell and Bradford (1948) describedsix cases, one being a severe pleuropulmonaryinfection which was cured by drainage of theempyema in conjunction with systemic penicillinand sulphadiazine. Six thoracic cases were des-cribed by Delarue and Houdard (1949) of whichfour were fatal, including one treated with 24 megaunits of penicillin. Rabin and Janowitz (1950)reported three cases of actinomycotic empyema,one having an underlying lung abscess. Theempyemata were cured by simple open drainage,while the third case required penicillin and radio-therapy in addition to drainage for its cure.

Since 1952 several reports have appeared in theliterature of cases treated by combined penicillinand sulphonamides (Scarinci, 1953; Rivas, 1952;Lawonn, 1953; Rumrich, 1953; Pttz, 1954;Nowski, 1953).

In a brief general review of thoracic actinomycosisDelarue (1954) recommends a combination ofpenicillin and sulphonamides as the most satis-factory treatment at the present time.

STREPTOMYCINMeurers (1951) was the first to report a case of

pulmonary actinomycosis successfully treated withstreptomycin and supronal, while Capitolo (1951)reports a similar case treated with streptomycinand P.A.S. Torrens and Wood (1949) reportedthree cases of actinomycosis treated with strepto-mycin, one being a thoraco-abdominal case inwhich a remarkable recovery took place whensurgery, penicillin, sulphonamides, and iodideshad previously failed. Blainey and Morris (1953)successfully treated a case of actinomycotic pyaemiaresulting from a pulmonary infection with a com-bination of streptomycin, penicillin, and sulphon-amides.

CHLOROMYCETIN, AuREoMYcrN, TERRAMYCIN, ETC.In some cases the Actinomyces israeli is highly

sensitive to these drugs, but the drugs in themselveshave disadvantages when given for the prolongedperiod which we consider necessary in the treatmentof thoracic actinomycosis. It is doubtful whetherit would be justifiable to give chloromycetin forthis condition, because of its possible adverse

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effect on the bone marrow, unless the particularstrain of Actinomyces israeli was insensitive to allother chemotherapeutic agents. Aureomycin andterramycin have other disadvantages, if given overa prolonged period of time, as we found ourselvesin the one case treated with terramycin. Littman,Paul, and Fusillo (1952) treated one case successfullywith chloromycetin for two months without anycomplications, and say that penicillin, aureomycin,and the sulphonamides are inadequate for a per-manent cure. Our results do not confirm thisstatement.

Ocklitz (1952) treated two cases successfullywith a combination of penicillin and aureomycin.Zoeckler (1951) treated one case with chest walland penrcardial involvement, also successfully, witha combination of penicillin and aureomycin.

Other cases have been treated with aureomycin(Heller, 1954; Reitter, 1954), combined aureomycin,erythromycin, and penicillin (Barker, 1954) andone by penicillin combined with potassium iodideCoenegrachts and Keil, 1954).Other examples have been published by Ayberk

(1953), Petfikova' and Van6cek (1953), and Sznajder(1953).

Cases treated by lung resection are described byReitter (1954) and Kugel, Harlacher, and Hueck(1953).

CLASSIFICATIONThe usual classifications of thoracic actinomycosis

have seemed to us unsatisfactory and we haveproduced an enlargement and modification of theexisting classifications. The nature of actinomy-cosis with its disregard of tissue barriers makesclassification difficult; for example, a primarypulmonary infection may spread through thepleura and chest wall, leaving an empyema andmultiple sinuses in its path. We have thereforeconcentrated upon the initial clinical picture withwhich the disease presented itself. The bronchiticand bronchopneumonic varieties have been omittedfrom this classification for the following reasons.Rare cases of the bronchitic variety have beendescribed in the literature (Canali, 1882; Cope,1938), but these have been of localized granulomataseen on bronchoscopy, and we do not believe thatan anaerobic infection can be confined to the wallof a bronchus without disease within the lungsubstance adjacent to that bronchus. On thesegrounds we have decided to omit the bronchiticvariety.

After study of these 85 cases we have foundthat actinomycotic bronchopneumonia only occa-sionally occurs as a complication of an existing

pulmonary infection, and we have no details ofany case presenting initially as a bronchopneumonia.We therefore present the following classification asa basis for study.

,maily pleuralPleuropulmonary /m pu

\mainly pulmonary/1lung abscess, single or multiple

PR\MARY-ronchopulmonary\simulating bronchial neoplasm

Mediastinal

/Extension from abdominal actinomycosisSECONDA&RY'/

\Extension from cervico-facial actinomycosisPyaemia

METASTATIC-Chest wall

CardiacACriNOMYCOsIS ASSOCIATED WITH PULMONARY TUBERCULOSIS

AETIOLOGYCope (1949) states: "We must put aside the

popular fairy tale about infections from grass andstraw." Primary infection of the lung is causedeither by the inhalation from a source within thebuccal cavity, or by spread through the bloodstream of the fungus Actinomyces israeli, which is ananaerobic or micro-aerophilic organism. Infectionwith the aerobic organism Nocardia asteroidesoccasionally occurs, and only one of the 85 patientsin this series was infected with this organism. Ithas been shown that the Actinomyces israeli is anormal inhabitant of many people's mouths andunder certain conditions of tissue damage orinfection in the lung the organism finds the necessaryconditions to invade the lung tissue and causesthe clinical condition of pulmonary disease. Onrare occasions the inhalation of fragments of cariousteeth have been reported as the cause of an actino-mycotic lung abscess (Israel, 1887; Roberts quotedby Cope, 1939).

Lingual actinomycosis was quoted by Bonnet(1921) as being the primary source of a thoracicinfection. Delarue and Houdard (1949) consideredthat the inhalation of infected material occurredfrom a lesion in the perilaryngeal tissues ratherthan from a carious tooth. In the present seriesthere is an increased incidence between the ages of10 and 20 and between the ages of 30 and 50. Weconsider that infection from the tonsils is animportant aetiological factor in the younger ofthese age groups, and dental sepsis in the older.Pleuropulmonary infections occurred frequently

in this series (44 cases). We believe that it isimportant to divide the pleuropulmonary infectionsinto two categories, those mainly pleural and thosemainly pulmonary; the prognosis ofcases presentingwith an empyema alone is better than those in

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FiG. W.H.1

which there is an empyema together with pulmonaryinvolvement. Bronchopulmonary infections were

less common and only 11 cases occurred. Medi-astinal infections may result from the entrance ofthe Actinomyces israeli through a mucosal lesionof the oesophageal wall; this lesion may subse-quently heal or occasionally persist as a broncho-oesophageal fistula. In mediastinal infections thedisease tends to spread to the vertebral column, tothe pericardium, and round both sides of thechest, presenting as bilateral chest wall or lumbarabscess.

Secondary extension from abdominal actino-mycosis is the second most common cause ofinfection in the chest, and 13 cases occurred inthis series. Generally the disease began in theileo-caecal region as an appendix abscess and latera subphrenic or liver abscess developed; theinfection then spread directly through the diaphragminto one or other of the lower lobes (Fig. W.H.1).

Secondary extension from cervico-facial diseaseis uncommon and only two such cases occurredin this series.Actinomycotic pyaemia is rare and generally

results from a pulmonary infection due to theanaerobic organism Actinomyces israeli, but caseshave been reported due to the aerobic organismNocardia asteroides; such spread through theblood stream invariably proved fatal before theintroduction of antibiotics.Pyaemia occurred in two of the 85 patients

under review.Chest wall lesions occurred in many of the

intrathoracic infections already mentioned, but insome instances the disease appeared localized tothe chest wall and did not invade the underlyingpleura, at least not in the first instance. Thedisease appeared to be confined to the chest wallin five of the patients in this series.

Infection of the heart or pericardium wasuncommon. There were two instances of peri-cardial involvement in this series, both from directextension of disease in the mediastinum. Therewas no instance of metastatic cardiac infection.

Cornell and Shookhoff (1944) collected from theliterature 68 cases in which the infection involvedthe heart or pericardium and added three of theirown, including one which presented as mitralstenosis and rheumatic fever. In 29 of these 68cases the infection resulted from direct extensionand in 19 by embolic spread from a distant focus.They state that it is unusual for the presentingclinical picture to be one of heart disease. In 1951Zoeckler collected a further eight cases includingone of his own, which, together with the two casesfrom the present series, makes a total of 78 casesreported.

COMBINED PULMONARY TUBERCULOSIS ANDAcTINOMYCOSIS

Von Arnim (1949) first described the combinedpresence of these two specific granulomata in apatient with a tuberculous cavity in the right upperlobe, the sputum containing tubercle bacilli. Latera substernal abscess developed from which typicalactinomycotic pus was obtained. The patientdied. We add two cases in which this combinationof disease was present. Both had tuberculousempyemata, Actinomyces israeli being present inthe pus in addition to tubercle bacilli. One patientrecovered following thoracoplasty, the other diedof amyloidosis five years after pleural drainage.Both these patients were treated in the pre-antibioticera.

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ILLUSTRATIVE CASESPLEUROPULMONARY: MAINLY PLEURAL

L. P., a male plastic worker aged 42, first complainedof severe bilateral chest pain in September, 1946. Thiswas later associated with dyspnoea and fever and hewas treated with sulphonamides. He then had ahaemoptysis, and radiographs of the chest in Octobershowed a large right pleural effusion from which 4 pintsof pus were aspirated; the fever slowly settled untilFebruary, 1947, when the empyema was drained. OnApril 17, 1947, he was transferred to another hospital,where the haemoglobin was 68% and the leucocytecount 17,250 per c.mm. Bronchoscopy was negative,and on April 28 the empyema was re-drained, the pusgrowing micro-aerophilic non-haemolytic streptococci.For three days before and 10 days after operation he

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FIG. L.P.2

Actinomyces israeli on anaerobic culture. His tempera-ture did not settle and on October 2 both empyematawere explored and further loculations of the cavitieswere found. The pus from the left side also grewActinomyces israeli, and after operation he was given asecond course of penicillin, 400,000 units a day foreight weeks, making a total of 23,400,000 units. Hequickly gained 20 lb. in weight and was discharged withboth empyemata healed. On February 5, 1948, hewas readmitted with breathlessness and pain in thechest. Radiographs showed a diffuse mottling through-out both lung fields (Fig. L.P.2). He was given a thirdcourse of penicillin, 1,000,000 units a day for 38 days,and again discharged having gained weight, though theradiographs showed only slight improvement. In July,

FIG. L.P. I

was given 200,000 units of penicillin twice daily, makinga total of 5,200,000 units. On June 21 a large sub-cutaneous abscess was drained in the right axilla; thisdid not appear to communicate with the empyemacavity. On July 12 he developed left-sided pleurisyand his sputum became blood-stained. He wasreadmitted to hospital 10 days later with clubbing ofthe fingers, which had not been present before, and hehad a left-sided empyema from which micro-aerophilicnon-haemolytic streptococci were grown (Fig. L.P.1).This was drained on August 1 and a large loculatedcavity containing fibrin was found. The left lungre expanded and he was discharged, only to be read-mitted on September 14 with marked dyspnoea and anabscess in the right axilla. This was drained of foul-smelling pus which contained sulphur granules and grew

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Fio. L.P.3

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1948, he had a further relapse and was readmittedwith persistent fever, cough with copious blood-stainedmucopurulent sputum, and severe pain in the chest.Dyspnoea was present on talking, and he had lostIj stones in weight since his last discharge. Radio-graphs showed a return of the diffuse mottling through-out both lung fields, and many specimens of sputumwere negative for tubercle bacilli, but occasionallyGram-positive filaments identical with Actinomycesisraeli were found. A fourth course of penicillin wasgiven; 1,000,000 units a day for 84 days, making acombined total for the four courses of 149,600,000 units.When last seen as an out-patient in August, 1956, heweighed over 13 stones and was fit and working. Hewas symptomless and a radiograph of the chest wasclear (Fig. L.P.3).

This case demonstrates the difficulty that maybe experienced in diagnosing this disease even whenit is suspected; seven months elapsed from thetime of drainage of the first empyema to thefinding of the Actinomyces israeli. The diffusemottling throughout both lung fields was theresult of a pyaemic spread from which the patientwould have died in the pre-penicillin era. It wasnot until he was given his fourth and only adequatecourse of penicillin that the disease was overcome.

PLEUROPULMONARY: MAINLY PULMONARYG. S., a commercial traveller aged 58 years, developed

a severe cold and dry cough in August, 1950. Threemonths later he complained of a continuous, dullaching pain between the shoulders and was treated forfibrositis. His general condition began to deteriorate

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FIG. G.S.1

FiG. G.S.2

and he lost 3 stones in weight. In December, 1950,he coughed up purulent sputum and remained in bedbecause of lassitude. He was admitted to hospital onJanuary 15, 1951, suffering from cachexia and coughingup 2 oz. of purulent sputum daily (Fig. G.S.1). Hehad an empyema necessitans presenting in the thirdleft interspace anteriorly ar.d was in pain. His teethwere carious and pus was exuding around the sockets.He weighed 7 stones and his tingers showed earlyclubbing. His haemoglobin was 46%. Stinking puswas aspirated from the empyema and both the pus andsputum contained sulphur granules and grew Actinomycesisraeli on anaerobic culture. A radiograph of the chestshowed diffuse mottling in the left upper lobe with afluid level in the pleura anteriorly and periostitis of thethird rib posteriorly (Fig. G.S.2). On January 20 hewas given a transfusion of 2 pints of fresh blood andpenicillin therapy was begun, 2 mega units of crystallinepenicillin being given eight-hourly. Within three dayshe had lost his pain, and after a week's treatment hehad no cough or sputum. His appetite returned andhe gained weight. A month later all his teeth wereremoved and he was discharged from hospital onMarch 22, having had a total of 365 mega units ofcrystalline penicillin. The haemoglobin was then 94%and he weighed 9 st. 12 lb. (Fig. G.S.3). A radio-graph of the chest showed incomplete clearing. Sixhundred thousand units of distaquaine penicillin dailywas continued at home for a total of 86 mega units.Since then he has returned to work and has remainedfit and well. A radiograph taken in June, 1956, showedcomplete clearing of the left chest.

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FIG. G.S.3

When this patient was first admitted to hospitalhe was moribund and his response to penicillintherapy was dramatic. The improvement in theradiographs did not keep pace with the improvementin his general condition, and it was at least a yearbefore they finally cleared.

BRONCHOPULMONARY: SINGLE LUNG ABSCESSJ. G., aged 24 years, a cabinet maker, developed

bronchitis with copious sputum in December, 1936.He was admitted to hospital and later developed a lungabscess in the right upper lobe. This was drained byrib resection and open drainage in April, 1937; hewas discharged in June, 1937, with the wound soundlyhealed. He remained well until March, 1938, when apainful swelling appeared over the left chest wallanteriorly and the patient became ill and anaemic. Aleft-sided empyema was drained and the tissues werefound to be oedematous and pockets of pus and granu-lation tissue were present. A streptothrix was seen inthe granulation tissue, while the pus contained sulphurgranules and grew Actinomyces israeli on anaerobicculture. Further operation was necessary and trackswere found running round from the anterior chest wallback into the erector spinae muscle. In April furtherribs were resected, and in June, 1938, there was a fouldischarge from the wound which resolved with zincperoxide dressings. The patient has remained well eversince, apart from occasional small haemoptyses due tothe resulting bronchiectasis, and in 1956 he was workingas an electrical contractor.Although there was no bacteriological information

about the pus from the lung abscess, there can be

little doubt that this and the ensuing empyemawere actinomycotic. It is interesting that suchextensive pulmonary and pleural disease shouldhave been eradicated by simple drainage in con-junction with zinc peroxide dressings.

D. H., aged 46 years, a garage attendant, developedpneumonia. Six weeks later he was admitted to hospital,by which time he had lost a stone in weight but hadno chest symptom other than a slight cough. A radio-graph showed a single cavity in the apical segment ofthe right lower lobe (Fig. D.H.I). Bronchoscopy wasnormal. A fluctuant swelling appeared over the righttrapezius from which pus was aspirated. The patientwas treated as a case of pulmonary tuberculosis. Hedied six weeks after admission. Necropsy revealedmultiple abscesses in the right lobe of the thyroid gland,both kidneys, and the right lung. Culture of pus fromthese grew a Nocardia astereldes.

FIG. D.H.1

BRONCHOPULMONARY: SIMULATING NEOPLASM

C. D., aged 44 years, a metal spinner, complained oflassitude and an aching pain in the right chest pos-teriorly, beginning in June, 1952. In September hedeveloped aching pains in the joints of all the limbs,but these disappeared after a month. Radiographs ofthe chest showed a diffuse opacity situated over theposterior part of the right upper lobe and apex of thelower lobe (Fig. C.D.1). A bronchoscopy was per-formed in October, 1952, as it was felt that he wasmost likely to be suffering from a bronchial carcinoma,but the bronchial tree was normal. The radiographsremained unchanged, and he was admitted to hospitalon November 11, 1952. On examination he was

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found to be in moderate health and to have earlyclubbing of the fingers. He had a morning cough witha little mucoid sputum. There was bronchial breathingover the whole of the right chest posteriorly and tomo-grams showed a rounded opacity in the apex of theright lower lobe which was considered to be a primaryperipheral bronchial carcinoma (Fig. C.D.2). Broncho-scopy was repeated and again the findings were negative.Clinical and radiological examination of his joints didnot reveal abnormalities. A right exploratory thorac-otomy was performed under penicillin cover onNovember 20. The lung was found to be so adherent

Fia. C.D.1

FIG. C.D.3.-The excised right lung is shown about half normal size.There is much fibrous thickening of the pleura posteriorly and oftheinterlobar septum. Severalconglomeratesofchronicabscesseswith pulmonary fibrosis are seen in both upper and lower lobes;the largest conglomerate, towards the hilum, simulated tumour inradiographs.

FIG. C.D.2

posteriorly that an extrapleural strip was necessary inorder to free it; when this had been done no localizedmass could be felt in the lung as the tomograms hadsuggested. As the fissures had become obliterated andthe disease appeared to involve the whole lung, a pneu-monectomy was performed. His post-operative coursewas uneventful, and a week later the lung was cut afterfixation and the naked-eye appearances suggestedpulmonary tuberculosis (Fig. C.D.3). Penicillin wasdiscontinued and streptomycin and P.A.S. substituted,until a week later when the histological report showedthe presence of pulmonary actinomycosis. Crystallinepenicillin was then given intrapleurally, and systemically2 mega units eight-hourly for a further six weeks. He

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was discharged, and 600,000 units of distaquaine peni-cillin given intramuscularly for a further six weeks,making a total of 287 mega units systemically and10 mega units intrapleurally. Since then the patienthas remained well and was last seen in January, 1956.Those cases which simulate bronchial neoplasm

are of particular interest to the thoracic surgeon.It is generally impossible to make a correct pre-operative diagnosis, and therefore pulmonary resec-tion is carried out, often with resulting broncho-pleural fistula, empyema, and spread of the disease.W'e would stress the importance of immediateexamination of the specimen in all undiagnosedresections so that if by chance it should prove tobe a case of pulmonary actinomycosis then adequatedosage of antibiotics can be given without delay,thus helping to avoid serious and often fatalcomplications.

MEDIASTINALK. W., aged 10 years, was first noticed to have a

painless swelling about 6 in. in diameter over the rightlumbo-dorsal region in December, 1939. She was alsobreathless on exertion and was admitted to hospitalwith an evening temperature of 100.5° F. This swellingwas incised and inspissated pus drained, the bacteriologyof which is not known. Later in the same month shewas given 0.5 g. sulphapyridine four-hourly for ninedays. On January 2, 1940, a rib was resected throughthe original incision; the pleural cavity was found tocontain blood-stained fluid, and a drainage tube wasinserted. By January 6 two additional sinuses hadformed and her general condition had deteriorated.On March 28, 1940, she was transferred to anotherhospital with a large right pleural effusion and a leuco-cyte count of 37,000 cells per ml. Thin fluid wasaspirated from the right pleural cavity in which noorganisms were seen on direct smear, and which wassterile on culture. Sulphur granules and Gram-positivefilaments were found in the discharge from the drainagesite. The patient was put on pot. iod., grains 30 perday, and discharged home. In July, 1940, she wasreadmitted to hospital with an indurated swelling overthe right eleventh rib which discharged spontaneously;the pus contained sulphur granules and grew Actinomycesisraeli on anaerobic culture. Radiographs in- August,1940, showed clouding over the lower half of the rightlung field, with periosteal reaction of the lower sixright ribs (Fig. K.W. I). The sinuses in the back werecuretted and the granulation tissue showed typicalcolonies of actinomyces. In November, 1940, bi-weeklyinjections of actinomyces vaccine were begun, andincreased to a dosage of 500 million fragments. Thetemperature quickly settled to normal and all the chestwall sinuses healed. The patient was discharged inDecember, 1950, while continuing with pot. iod., grains30 t.d.s. In January, 1941, sinuses reopened, and in Mayshe began to lose weight and developed a continuous

Fio. K..WI

cough. She was readmitted to hospital in September.1951, in poor general condition and suffering discomfort,but no pain, from multiple sinuses on both sides of theback. There was marked flattening of the right chest withsevere scoliosis to the left side. The sinuses in the back, ofwhich there were at least 30, were each surrounded bydark reddened skin of indolent appearance. Radio-graphs of the chest at that time showed wideningof the mediastinum not unlike the appearance ofa mediastinal sarcoma. The patient never complainedof pain but steadily wasted and died on December 1,1941. Post-mortem examination showed completeinvolvement of both lungs with actinomycosis. Theoesophagus was found to be intact but surrounded byfibrous tissue. The liver and spleen were congestedand showed the typical picture of amyloid disease.

T'his case illustrates several important charac-teristics of the disease. The first specimen of puswas sterile on culture and only later was the diag-nosis confirmed by anaerobic culture and sectionof the granulation tissue. The fornation of multiplechest wall sinuses which healed and broke downagain is typical. The periosteal reaction of severaladjacent ribs in the absence of an empyema is theonly radiological appearance which is pathogno-monic. Pain, which is generally a feature, wasabsent in spite of many chest wall sinuses. Post-mortem examination showed amyloid disease inthe liver and spleen, a condition often associatedwith actinomycosis. The marked improvementwhile the patient was having vaccine therapy is inagreement with the experience of other workers,but almost invariably a relapse occurs. Themarked peri-oesophageal fibrosis which was foundat necropsy may have been the reaction to the

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primary portal of entry of the actinomyces througha temporary abrasion in the oesophageal mucosa.

EXTENSION FROM ABDOMINAL AcTINOMYCOSIsWe have included two case histories under this

heading. The first is an example of abdomino-thoracic actinomycosis originating in an appendixabscess; the second resulted from abdominaltrauma and was one of the first cases to be treatedin this country with penicillin.

Mrs. I. W., aged 49 years, a housewife, had a per-forated appendix removed in September, 1941, and wasdischarged a month later with her wound healed. InNovember, 1942, she developed a right-sided empyemawhich was drained by rib resection and she was dis-charged with the wound healed in April, 1943. InMay, 1943, she developed abscesses in the right groinand umbilicus. These subsided on conservative treat-ment until December, 1943, when the groin abscessrequired incision and drainage. Omentum was liningthe deep surface of the abscess and there were manysinuses extending into the abdominal wall. In May,1944, a further abscess was drained and found toinvolve the rectus sheath. In September, 1944, shedeveloped pneumonia and was treated at home withsulphapyridine until October 5, when she was readmittedto hospital with a large left pleural effusion containingno organisms and sterile on culture. She was coughingup 1 oz. of mucopurulent sputum daily, but the fingerswere not clubbed. There were multiple dischargingsinuses in both lower quadrants of the anterior abdominalwall. Aspiration of the chest produced straw-colouredfluid, and both this and the sputum contained typicalsulphur granules which grew Actinomyces israeli onanaerobic culture. The pleural fluid later becamepurulent and offensive. Intramuscular penicillin wasbegun on November 17 and 200,000 units was givendaily until December 6 when a total of 3,800,000 hadbeen given. The empyema was also aspirated on eightseparate occasions and a total of 346,000 units of peni-cillin was injected into the pleural cavity. The indura-tion of the abdominal wall had disappeared and allthe sinuses had healed; on January 11, 1945, theempyema was drained by rib resection. In May, 1945,she complained of pain across the shoulders, andcoughed up some blood-stained sputum which con-tained sulphur granules; systemic penicillin was begunon June 1 and 200,000 units was given daily until June 22when 4,200,000 units had been administered. She wasdischarged in July with a tube still in situ. She wasreadmitted on October 1, 1945, feeling very fit, butcoughing up 1 oz. of purulent sputum daily which stillcontained the typical Gram-positive branching filamentsof Actinomyces israeli. Her general condition wasexcellent and the abdominal sinuses had remainedhealed. A third course of systemic penicillin wasbegun and 280,000 units was given daily for aboutthree weeks, making a total of 5,880,000 units, and forthe three courses of 13,880,000 units. She was dis-

charged on November 23, 1945, in spite of still havingActinomyces israeli in the sputum; the latter wereevident until May, 1946, when the cough and sputumfinally ceased. In October, 1946, the sinus had nothealed, and the small residual empyema cavity wastherefore re-drained. Section of the thickened pleuradid not show actinomycosis or tuberculosis. OnDecember 12, 1946, there was still a small residualempyema cavity, which was finally closed by a Robertsoperation. The patient was discharged with all woundshealed on January 5, 1947, and when she last attendedas an out-patient on March 5, 1956, she appeared inexcellent health without cough or sputum, and all thewounds had remained healed.

This case illustrates the time interval which mayelapse, and may be as long as two years, betweenthe abdominal and thoracic infections in thisdisease. This patient's disease was protracted bythe three short courses of penicillin which shereceived and by the small total dosage.

C. B., aged 22 years, a police clerk, while serving inthe Army had a hand grenade, which he was holdingin his left hand, detonated by a bullet on November 2,1943. The left arm was blown off above the elbow andthe left chest wall was riddled with small pieces ofmetal, a small fragment penetrating the abdomen andgiving rise to a pneumoperitoneum. He recoveredfrom these wounds, but while on disembarkation leavedeveloped severe pain in the back and was admittedto hospital on January 12, 1944. On examination hehad a temperature of 1030 F. and a tender swellingover the left eleventh rib. This was explored, but nocause found; a week later a portion of the eleventhrib was resected and a localized subphrenic abscesswas drained. After drainage he was given a courseof sulphadiazine and several fresh blood transfusions;his temperature remained unsettled and in March,1944, a left lumbar abscess was incised and offensive,thick pus was found to be tracking from the perinephricregion, as well as from the previously drained subphrenicabscess. In April a collection of pus was drainedbeneath the left costal margin. Afterwards he wasgiven another course of sulphamezathine and the leftchest was needled in many places but no pus found.On May 23, 1944, he was transferred to another hospitaland on examination looked thin and pale with a tem-perature of 1000 F. He produced 3 oz. of purulentsputum daily, but the fingers were not clubbed. Hedeveloped more sinuses around the left costal margin,and finally sulphur granules were found in the dischargeand in the sputum, both of which grew Actinomycesisraeli on anaerobic culture in the presence of carbondioxide, this particular strain being fully sensitive topenicillin. Radiographs at that time showed metallicforeign bodies and an opacity in the region of the leftlower lobe; the left diaphragmatic outline was obscured.A sinogram demonstrated the ramifying subphrenicabscess and three external sinuses. By the end ofJune his general condition was deteriorating and therewas loss of weight. He had been running an evening

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temperature up to 1010 F., and was coughing up 3 to5 oz. of purulent blood-stained sputum daily. OnJune 26 systemic penicillin was begun and 120,000 unitsgiven daily for 15 days. His temperature fell to98.40 F. in the evenings, and by the eleventh day hiscough and sputum had disappeared. On June 26 heweighed 9 st. 4 lb. and was allowed to get up, but 10 dayslater his temrerature rose again and the discharge fromthe sinuses increased. He was given a course ofsulphamezathine for four days and then systemicpenicillin was started again, 200,000 units being givendaily for 30 days. The total dosage for the two courseswas 7,800,000 units. On completion of treatment thesinuses had healed and he weighed 10 st. 10 lb. Sincethen he has attended as an out-patient, and when lastseen, in October, 1956, he was working as a policemanand weighed 13 stones. He has had no further troublewith his chest and a radiograph shows complete clearingof the left lung field, except for obliteration of the costo-phrenic apgle and a residual metallic foreign body.This patient's history, previously reported by

Roberts and others (1945), demonstrates the dangerof a relapse if therapy is discontinued as soon asa satisfactory clinical response has been obtained.In the week before starting penicillin therapy thisman was dying, and 12 years later he is cured ofthis disease.

EXTENSION FROM CERVICO-FACIAL ACTINOMYCOSISJ. W., aged 43 years, a painter and decorator

developed a cold and pleuritic pain in the right chestin April, 1949. Radiographs showed a right pleuraleffusion, and he was admitted to hospital on July 22,1949. He gave a history of an actinomycotic infectionof the right side of the jaw in 1938, and had had treat-ment with iodides and penicillin on various occasions.The right temporo-mandibular joint was almost com-pletely ankylosed and there was a discharging sinusover the jaw. He was in good general condition andthere was no clubbing of the fingers or history ofhaemoptysis. The sputum was negative on severaloccasions for both tubercle bacilli and mycelial filaments.It was impossible to bronchoscope the patient as hisjaw would only open for J in., but a tentative diagnosisof carcinoma of the right lower lobe bronchus was made.A right thoracotomy was performed on August 9,1949, when the pleura was densely adherent and arubbery mass felt in the middle and lower lobes. Therewere no enlarged mediastinal glands and a right middleand lower lobectomy was done. The day after operationthe patient developed a high fever and the pleural fluidgrew a penicillin-resistant Staphylococcus aureus. Despitepenicillin therapy a bronchopleural fistula developed onthe tenth day and was followed by fatal aspirationpneumonia.At necropsy the central part of the lower lobe contained

a firm, greyish-white tissue stippled with carbon pigment.There were many subpleural yellowish areas resemblingsmall foci of a variable degree of fibrosis of thesurrounding lung tissue. Histological section showed

areas of acute and chronic inflammation, the lattercontaining masses of granulation tissue heavily infil-trated by round cells. There were also several smallbronchopneumonic abscesses, and in the centre ofseveral of these mycelial colonies were seen Gramn-positive filaments identical with Actinomyces israeli.The left lung revealed a confluent staphylococcalbronchopneumonia with multiple abscess formation, inone of which there was a matted mycelium of Gram-positive branching filaments.The pulmonary infection which followed 11 years

after infection of the jaw may have spread, bydirect extension by way of the tissues of the neckand thoracic inlet, or by inhalation to the basalbronchi from the mouth. This demonstrates anunusual diagnostic difficulty. Bronchoscopy, whichwas prevented by the ankylosis of the temporo-mandibular joints, would have led to the correctdiagnosis and subsequent therapy with systemicpenicillin, thus obviating surgery in this phase ofthe disease.

METASTATIC: PYAEMIAC. C., aged 42 years, a fitter, complained of pains in

the calf muscles in January, 1947. He was admittedto hospital in March and a series of abscesses wasopened in both legs, buttocks, back, and chest wall.In April he developed a left-sided pleural effusion withconsolidation of the left lower lobe. He was treatedwith N.A.B. and a staphylococcal vaccine without anyimprovement. In December, 1947, a clinical diagnosisof actinomycotic pyaemia was made as no specificorganisms had then been isolated and a course ofI mega unit of crystalline penicillin daily was given forsix weeks. This resulted in improvement in his clinicalcondition, but healing of all the sinuses was onlyobtained after a course of radiotherapy. During thistreatment a micro-aerophilic Actinomyces israeli waseventually cultured. He remained fit until July, 1952,when he complained of pain in the left upper chestassociated with cough and purulent sputum. In Augusta radiograph showed an opacity at the left apex whichwas thought to be tuberculous and he was admittedto hospital in October, 1952 (Fig. C.C.1). His generalcondition was good, although his haemoglobin was 77%and his fingers showed early clubbing. He was coughingup I oz. of purulent sputum daily, which grew a micro-aerophilic Actinomyces israeli morphologically andculturally similar to the organism found in 1947. Hewas given a six weeks' course of 2 mega units of crystal-line penicillin eight-hourly; after five days of thistreatment his pain had disappeared and he had nocough or sputum. This course was followed by afurther six weeks of 600,000 units of distaquaine peni-cillin daily, making a total continuous course of 273 megaunits. He was discharged in December, 1952, and hasremained well and at work ever since. He last attendedthe Out-patient Department on July 25, 1956, when achest radiograph was clear.

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FIG. C.C.1

FIG. M.B.1Actinomycotic pyaemia is rare and generallyresults from infection with the anaerobic organismActinomyces israeli; cases have been reported dueto the aerobic organism Nocardia asteroides.Spread by the blood stream invariably proved fatalbefore the introduction of antibiotics.

METASTATIC: CHEST WALLM. B., aged 10 years, complained of feeling tired in

February, 1947. An abscess later developed on theleft anterior chest wall, and she was admitted to hospitalwhere this abscess was drained and what was thoughtto be a tuberculous rib resected. The wound did notheal, and when she was readmitted to hospital in Feb-ruary, 1948, there were several granulating areas overthe lower half of the chest wall anteriorly (Fig. M.B.1).These granulating areas were tender and histologicalsection from a biopsy showed the typical colonies ofActinomyces israeli. She weighed 4 st. 7 lb. and herhaemoglobin was 80% before treatment was begunwith daily intramuscular injections of 1 million unitsof penicillin for 21 days. The granulating areasdiminished in size and healed (Fig. M.B.2). She beganto put on weight and her general health improved.Her condition has remained satisfactory up to 1956.

This case illustrates the typical chest wall lesionsand emphasizes that they are usually extremelypainful. FIG. M.B.2

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Fio. R.H. I

PULMONARY TUBERCULOSIS AND ACTINOMYCOSISR. H., a man of32 years, developed bilateral pulmonary

tuberculosis in India in October, 1944. His sputumwas positive for tubercle bacilli. In February, 1956, aright artificial pneumothorax was induced and twothoracoscopies carried out. In March, 1946, he had aphrenic crush. In October, 1946, he developed multiplesinuses in the chest wall. He returned to Great Britainin January, 1948, and at this time thick pus was aspiratedfrom the chest from which anaerobic Actinomyces israejiwas cultured (Fig. R.H.1). The pleura was drainedand a thoracoplasty carried out in October, 1948. Thewound was healed five months later. This man hasremained well with no evidence of active disease in thechest.

This case illustrates the simultaneous occurrenceof two chronic granulomata; the actinomycoticinfection remained confined to the pleural cavity.

EPIDEMIOLOGY AND PATHOLOGYGEOGRAPHICAL INCIDENCE

Thoracic actinomycosis has been reported frommany different countries, but particularly fromEurope and the United States of America. Poncetand Berard (1898) reported a high incidence inGermany, and Robinson and Tasker (1949) ahigher incidence in southern California than inother states of America.

OCCUPATIONAL INCIDENCEFor many years the view was held that country

dwellers were more prone to this condition than

town dwellers. This may be true in the case ofcervico-facial disease, but it is not so for pulmonaryinfections. In this series there were 80 towndwellers and five country dwellers.

THORACIC INCIDENCEAll authors agree that approximately 15% of

human actinomycotic infections affect the thorax(Poncet and Berard, 1898; Bell, Mantell, Netzer, andJaffe, 1944; Foulerton, 1913; Cope, 1930). Sokolow(1889) reported a 30% thoracic incidence fromRussia, while Harbitz and Grondahl (1911) found a23% incidence in 87 cases from Norway.

It has been thought that the majority of thoracicinfections have resulted from secondary involvementfrom the abdomen, and Good (1930) reported 15out of 16 thoracic cases to be secondary in origin.We have not found this to be so in the presentseries, in which 70 were primary infections withinthe chest and 15 the result of secondary spread.

AGE AND SEX INCIDENCEMales are affected more often than females, and

various figures are quoted, ranging from 4: 1(Sanford and Voelker, 1925; Schmitt and Olsen,1941) to equal proportions (Colebrook, 1921). Inthe present series three times as many males asfemales were affected. The majority of cases occurafter the age of 20 (Good, 1930); but the diseasecan start at any age and the youngest reportedcase was a child of 28 days who died from an actino-mycotic lung abscess (Lemon, 1926). In thepresent series the youngest patient was a girl of31 with a lung abscess, and the oldest a man of76 with an empyema.

0-10 11-20121-30 31-4041-50{51-60 61-70 71-80Age incidence .. 6 17 8 19 22 9 2 2

Sex Males: 64 Females: 21

MORBID ANATOMY AND HISTOLOGYPulmonary actinomycosis is a chronic disease

which simulates pulmonary tuberculosis, and themorbid process is usually far advanced when theearliest symptoms become manifest. The primarylesion is either in the bronchioles, or in the peri-bronchial tissues, or in the lung parenchyma; itis suppurative and proceeds to abscess formationthat may be extensive and is attended by inter-stitial pneumonia with fibrosis. The initial lesionis seldom seen save when one or more lung lobulesbecome infected from an adjacent abscess. Thenthe lesion is bronchopneumonic-of the chronicsuppurative type-with marginal pneumonia that

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..

:a

FIG I

P.

FIG. 5

FiG. I.-A colony of actinomyces in the lung. In the centre is adense mass of mycelial filaments; the periphery shows verydistinct radially arranged" clubs "stained red. The surroundingcells are polymorphonuclear leucocytes. Haemalum and eosin,

e350.

FiG. 2.-A colony of actinomyces in the margin of a suppurativefocus in the lung. Most of the surrounding cells are polymorphleucocytes; a few pigmented macrophages are present. Haema-lum and eosin, x 75.

FIG. 5.-This sputum shown Gram-positive branching mycelialfilaments among pus cells. Gram's stain, x960.

Fio. 2

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later organizes with resulting fibrosis. The diseaseprogresses thus, from lobule to lobule, and byextension of the suppurative process by continuity,so that eventually multiple abscesses with inter-vening dense fibrous tissue occupy a large part ofa lobe and may present as a coarse honeycomb,an appearance that is characteristic of this diseasewhen it occurs in the liver.

Actinomycosis is described as occurring morefrequently in the lower than the upper lobe, butboth or all lobes of a lung may be affected andmore than one segment of a lobe may be involved.Thus in the case illustrated (Fig. C.D.3) there aresmall subpleural chronic abscesses, with fibrosis ofthe lung, in the apical segment of the upper lobeand the apical segment of the lower lobe. Inaddition, in the posterior segment of the upperlobe there is a more extensive conglomeration ofsuppurative foci comprising distinct abscesses,suppurative bronchopneumonic lesions some ofwhich are progressing to abscess formation andaccompanying fibrosis. So compact was this largeconglomerate that radiographically it was con-sidered to be a tumour near the hilum.The pleura is involved and becomes thickened

and fibrosed, especially in relation to subjacentsuppuration when local intrapleural abscesses orempyema may result. But even in the absence ofsuppuration immediately near the pleura, the latterbecomes fibrosed and thickened in the same wayas the fibrous tissue septa of the lung that connectwith it become fibrosed from extension of theinterstitial pneumonic fibrosis. The peribronchialfibrosis results from the same inflammatory process.

Histologically all the features of the disease asdescribed are seen-the chronic suppurative fociwith marginal pneumonia that later organizes withresulting fibrosis, suppurative bronchopneumonia,etc. Some of these histological features are illus-trated in the accompanying photomicrographs(Figs. 1, 2, 3, 4). The pus in the abscesses is mainlypolymorphonuclear, although round cells andmacrophages, some with haemosiderin and otherpignents, are present. The characteristic anddiagnostic feature is the presence of one or morecolonies of actinomyces that can be seen in routinesections, stained with haemalum and eosin, with thesame ease or difficulty that attends their discovery as" sulphur granules " in pus from lung or otherabscesses, or from sinus tracks. The colonialappearances are distinctive; the central loose ordense mass of branching mycelial filaments isstained blue with haemalum; the peripheral,radiate, club-like swollen outer ends of the filamentsare stained red with eosin (Figs. 1, 2). The colonies

FIG. 3.-The suppurative process has destroyed all but one part ofthe wall of this bronchus; the columnar epithelial lining remain-ing is seen on the left of the lumen, which is otherwise occupiedby pus cells. Adjacent alveoli show cellular exudate. The wholepicture is one of suppurative bronchopneumonia. Haemalumand eosin, x 150.

FIG. 4.-These alveoli near a suppurative focus (lower left) show thecontained exudate being organized by ingrowing capillaries andfibroblasts. This granulation tissue leaves a residue of fibroustissue which condenses to form the diffuse fibrosis aroundsuppurative foci. Haemalum and eosin, x 150.

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are easily identified in Gram-stained preparationsor in sections stained by a modified Ziehi-Neelsenmethod.The sputum in patients suffering from pulmonary

actinomycosis is often purulent and may containcolonies of the organisms as " sulphur granules";more frequently, however, branching mycelialfilaments may be found (Fig. 5).

COMPLICATIONSMicrocytic anaemia which is occasionally severe,

is a common complication of thoracic actino-mycosis.

Cerebral abscess and pyaemia are rare complica-tions and the primary infection is usually in thethorax (West, 1897; Lidbeck, 1942); they areparticularly liable to occur when there is cardiacinvolvement (Dean, 1912).Amyloid disease develops in those patients who

have a long history of thoracic actinomycosis, andoccasionally may occur as an acute condition earlyin the disease (Tubbs and Turner, 1937).

PHYSICAL SIGNS AND SYMPTOMSSIGNS

The only physical sign which could be describedas diagnostic for this condition is the nature of thechest wall sinus. The sinus tends to heal over fora few days and then breaks down and dischargesagain (Fig. F.T.1). Sulphur granules can occa-sionally be seen with the naked eye in the discharge,and the granulation tissue around the sinus isexuberant, vascular, and painful to touch. Witha chronic pyogenic empyema a sinus may appearand remain single for many years, but in thoracicactinomycosis there is generally multiple sinusformation at an early stage.

Fic. F.T.1

SYMPTOMSPain is the common presenting symptom, and

43 cases in this series started in this way. Thereare four different types of pain from which thesepatients suffer, depending upon the variety of thedisease. Pleuropulmonary infections in which thepleural cavity is obliterated often present withrheumatic pain, while those who have an empyemamay present with an acute pleurisy. The mediastinalcases complain of a continuous retrosternal aching,while the chest wall lesions are painful to touch.Cough occurs at some stage of the disease, and

is associated with purulent sputum.Haemoptysis is unusual; but large haemoptyses

can occur when a lung abscess is present.A few cases presented with lassitude before

chest symptoms developed.

DIAGNOSISCLINICAL

The clinical manifestations of thoracic actino-mycosis are protean. The diagnosis may be simplein cases presenting with characteristic painful chestwall sinuses; sulphur granules may be seen inthe discharge, bacteriological examination of whichmay reveal the causal organism. Biopsy from thesinus may demonstrate the characteristic tissuechanges of actinomycosis. Similarly, cases present-ing as empyemas may be easy to diagnose. Butmany present with indefinite symptoms and bizarreradiological appearances; it is in this group thatdiagnostic difficulties arise. It may be impossibleto arrive at a definite diagnosis until material isobtained for examination at thoracotomy. Despitethis, we urge that an attempt be made to reach adiagnosis before chemotherapy or antibiotics areused in treatment, because once these have beenadministered the difficulties of making an accuratediagnosis can be increased. This is illustrated bythe following case:

A. B., a girl of 22 years (Fig. A.B.I), developed aproductive cough, rapidly followed by pain in thechest and thickening in the tail of the right breast. Aweek later there was a hard mass in the breastand a tentative diagnosis of sarcoma was made. Atthis time she showed a radiological opacity in theright upper lobe. Her sputum contained no pathogenicorganisms. Penicillin was given for three weeks, andafter this the breast mass disappeared and the pulmonaryshadow diminished. Two weeks later the breastswelling returned and an abscess discharged spontane-ously; the pus from this abscess grew Actinomycesisraeli. Further penicillin was then given, resulting incomplete healing.

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THORACIC ACrINOMYCOSIS

abdominal sinus passed through the diaphragm into themiddle lobe. This man was cured by penicillin therapy.The following case illustrates another difficulty

which may be encountered.E. M., a woman of 49, developed a morning cough,

followed two months later by haemoptysis. Whenfirst seen four months after the onset of symptoms shewas dyspnoeic and had lost weight. A radiographtaken in November, 1949, showed a left hilar opacitywith collapse of the lingula and an ovoid right lowerlobe shadow (Fig. E.M.1). Bronchoscopy was normaland sputa were negative for tubercle bacilli and malig-nant cells. The diagnosis made at this time was bron-chial carcinoma with a metastasis in the right lowerlobe. Five months later she developed chest wallabscesses. Pus aspirated from these gave a culture ofActinomyces israeli. She recovered completely withpenicillin therapy.

FiG. A.B.1

Thoracic actinomycosis may, by involvement orirritation of lower intercostal nerves, cause abdom-inal pain and simulate upper abdominal disease.A man of 20 was admitted to hospital with acute

epigastric pain, and a diagnosis of right anterior sub-phrenic abscess was made. The abdomen was exploredwith negative findings. After the wound had healed hedeveloped chest pain, and radiographs showed middlelobe consolidation (Fig. D.L.1). The wound broke downand discharged foul pus from which Actinomyces israel'iwas grown. This organism was also cultured from hissputum. Lipiodol injection demonstrated that the

FIG. E.M.1

BACTERIOLOGICALThe technical details of laboratory diagnosis

have been described by Garrod (1952b). We areconcerned in an attempt to indicate certain basicrequirements necessary before a diagnosis of clinicalthoracic actinomycosis can be made on the basisof bacteriological findings. The finding of actino-myces in the sputum or in bronchoscopic aspirates

X does not necessarily mean that the patient is sufferingfrom actinomycosis. Actinomyces israeli is a normal

FIG. D.L.1 inhabitant of many human mouths, in dental tartar,

K

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tonsillar crypts, and carious teeth. Kay (1947)reported finding actinomyces in 109 of 240 casesof pulmonary suppuration and also stated thatapproximately 50% of bronchiectatics have actino-myces in their sputum. Many of these had resec-tions carried out without untoward complications.We believe that this is a misconception of thedisease and that in these patients the actinomycesplayed no part as pathogens. As has already beenshown, the tissue response to actinomycotic infec-tion is specific, and unless this can be demonstratedin an excised portion of tissue the diagnosis is nottenable. Garrod (1952b) has emphasized thatsputum for bacteriological examination should firstbe washed to eliminate saliva and mouth organisms.In his series of 40 cases of pulmonary suppuration15 yielded no actinomyces on culture from washedand unwashed material, 25 grew an actinomycesfrom an unwashed but not from a washed inoculum,while nine grew an organism from both. Theactinomyces cultured in this series had the charac-teristics of the aerobic form Actinomyces naeslundi.Garrod goes so far as to state that unless thesputum contains actinomycotic granules it is doubt-ful whether a diagnosis should ever be made onsputum findings or even on bronchial aspirates.The examination of pus in bulk may reveal thesulphur granule, and by staining methods andanaerobic culture of these the specific organismActinomyces israeli may be identified. In the veryrare cases in which clinical pulmonary infection isdue to a nocardia the organism will be grown byaerobic culture.

RADIOLOGICALMany radiological appearances have been des-

cribed as typical of puhmonary actinomycosis.These assertions are not supported by the facts ofthe present study. The only characteristic radio-logical changes produced by thoracic actinomycosisare the result of bone change. These were firstnoted by Staub-Oetiker (1921), who describedperiostitis of several adjacent ribs in the presenceof a pulmonary infection without empyema. Theseappearances enabled the radiologist to make acorrect diagnosis in the case cited (Fig. A.E.1).Bone involvement with actinomycosis results in

bone destruction simultaneously with new boneformation. Fig. F.T.2 shows sternal involvementin a man who had suffered from actinomycosis ofthe chest wall for many years; he died of secondaryhaemorrhage from the internal mammaiy artery.The radiological appearance of the lungs is notdiagnostic. Since 1921 several authors, includingKoerth, Donaldson, and Pinson (1942) and Kirklinand Hefke (1931), have described the radiological

Fia. A.E. 1

appearance of thoracic actinomycosis, but none hasconsidered any appearances ofdiagnostic significanceother than periostitis of several adjacent ribs inthe absence of an empyema. With these findingswe are in full accord, and would urge that thepossibility of actinomycosis be kept in mind whenconsidering the significance of puzzling shadows inchest radiographs.

_'i"~~~~~~~~~~~~~~~~~~0-: X.

FIG. F.T.2

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TREATMENTGENERAL MEAsUREs

Many patients suffering from actinomycosis arein poor general condition as the result of long-continued infection and pain. They may be anaemicand have lost weight as a result of protein depletion.In the present series a haemoglobin reading of aslow as 50% to 60% was commonly obtained beforespecific treatment was begun. Adequate proteinand vitamin intake together with fresh bloodtransfusion or administration of iron as indicatedare of importance. Pain is relieved as soon aspenicillin has been administered.

SPECIFC MEASURESWith the advent of chemotherapy and antibiotics

many of the treatments previously employed havebecome obsolete. Various sulphonamides havebeen used in the treatment of thoracic actinomycosis-where one failed success was often achieved by acombination of others and particularly by simul-taneous administration with penicillin. At thepresent time sulphonamides have been replaced bypenicillin as the treatment of choice.

CHLORAMPHENICOL, AUREOMYCI, TERRAMycIN,AND ACHROMYCiN.-We have no experience of theuse of chloramphenicol or aureomycin in treatingthoracic actinomycosis. The danger and discomfortto the patient attendant on the use of these drugsover a long period make us feel that it would beunjustifiable to employ them in preference topenicillin. The same objections apply to terramycinor achromycin, both of which are liable to causediarrhoea and possibly serious staphylococcalenteritis. Terramycin has been used as an adjunctto penicillin in two cases in the present series. Inone of these the patient maintained that the chestwall sinuses remained healed for longer with thisdrug than with peniciUin. Penicillin is the mosteffective agent yet produced. In the earlier casesin this series relatively small doses were used, yetmany of these patients were cured. Many more,however, showed temporary improvement only andlater relapsed. In the present series relapses haveoccurred in patients having as much as 4 megaunits of penicillin daily. We feel that it is importantto give a sufficient dosage for long enough to makecertain of curing the patient at the first attempt.We recommend for an adult 6 mega units of crystal-line penicillin daily (2 mega units eight-hourly)during the period in hospital (six weeks), followedby an out-patient course of 600,000 units dailyfor a similar period, making a total of 277 mega

units over a three-month period. Cases treated inthis way have shown neither relapse nor sensitivityreaction. In children the dosage will requiresuitable modification.STREPTOMYCIN.-We have no personal experience

of the exclusive use of this drug in the treatmentof actinomycosis. Studies in vitro by Boand andNovak (1949) demonstrated that penicillin has agreater effect on Actinomyces israeli than hasstreptomycin. These authors conclude that, inview of the long duration of antibiotic treatmentnecessary in actinomycosis, the risk of developmentof streptomycin-resistant strains would be high.Garrod (1952a) has studied the effect of five

different antibiotics in vitro upon 12 strains ofActinomyces israeli. The therapeutic response to aparticular antibiotic in vivo is more to be relied onin the treatment of actinomycosis than its behaviourin vitro suggests. Again, in view of the long-continued treatment necessary, we reiterate thatpenicillin is the drug of choice. We do not inferthat studies in vitro are valueless, but that theymay be misleading. The development of an insensi-tive strain of organism during antibiotic therapy isa source of anxiety, and one case in our seriesdemonstrates that this may happen despite adequatetherapy.D. S., a man of 17 years, had an actinonycotic

subphrenic abscess drained. Actinomyces isra?li cul-tured from the pus was sensitive to penicillin (inhibitingconcentration 0.029 units per ml.). He was treatedwith penicillin (100 mega units in 10 weeks), but hiscondition deteriorated. Further sensitivity tests at thistime showed that the organism was now approximately10 times as resistant as it had been at the beginning oftreatment. This man eventually died from acuteamyloid disease and had actinomycotic abscesses inboth lungs, liver, and abdominal wall.The clinical response to penicillin may be excel-

lent even with strains of Actinomyces israeli resistantin vitro.

SURGICALThirty patients in the present secies had some

form of surgical treatment. In many of these thediagnosis was not known at the time of operation.The majority had empyemas (20 cases); sevenpatients were treated by lung resection.EMPYEMA.-A variety of methods were employed.

The majority were straightforward empyemas, butone followed pneumonectomy for a non-actino-mycotic lung abscess, while two were associated withtuberculous pyothorax. There were no deaths in thecases in which penicillin was used as an adjunct tosurgery. Simple drainage was employed in seven

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FIG. A.F.1

cases, one of which followed pneumonectomy.This man was alive and well three years after opera-tion but cannot now be traced. Of the remainder,only two recovered, one of whom is well 13 yearslater. The other died of primary carcinoma ofthe colon five years after heaLing of the empyema.In the pre-penicillin era it seems likely that simpledrainage of an actinomycotic empyema was curativeif the lung lesion was of small extent and accessibleto the oxygen available in the pleura, as for examplewhen the empyema was due to rupture of a smallsubpleural lung abscess. This is exemplified bythe following case.A. F., a man of 53 years, gave a two months' history

of pain in the chest, cough, and purulent sputum. Hewas admitted to hospital in 1942 with an encystedeffusion and bronchopleural fistula (Fig. A.F.1).Actinomyces israeli was grown from both sputum andpleural pus. The empyema was drained and a smallperforated lung abscess was seen. Final healing tookplace in May, 1943, seven months after drainage. In1948 he died of carcinoma of the colon, proved bylaparotomy. He had had no trouble with his chestsince the healing of the empyema.

Drainage combined with penicillin was used inseven cases and is the standard method of treatment.All these patients were cured. The treatment ofthe empyema differed in no way from the usual.

J. McC., a man of 76 years (the oldest case in theseries), was admitted in September, 1953, for incisionof a chest wall abscess. Radiographs showed anencysted basal effusion with an inflammatory process inthe right lung. Actinomyces israeli was grown from theabscess. He was treated by penicillin for four weeksand drainage of the empyema, with a good result.ASPIRATION wITH INTRAPLEURAL PENICILLIN RE-

PLACEMENT.-We have records of three cases ofempyema treated by aspiration and intrapleuralpenicillin, combined with systemic penicillin. Inone of them streptokinase and streptodornase wereused in addition. All are classed as cured.

E. B., a man of 34 years, was first seen in 1947 withhaemoptysis, which was rapidly followed by dyspnoeaand chest pain. He was admitted with a total leftempyema from which 4i pints of pus were aspiratedcontaining Actinomyces israeli (Fig. E.B.1). Systemicpenicillin was given for two weeks (total, 7 mega units).Eleven pleural aspirations were carried out with instil-lation of 300,000 units of penicillin on each occasion.He was discharged after three months in hospital. Hewas well in January, 1954, and was working as abrewer's drayman (Fig. E.B.2).

EXCI ION OF EMPYEMA.-One case has been treated inthis way, a boy, D. H., aged 12, who developed a chestillness a week after tonsillectomy and adenoidectomy.Twenty-two days after the tonsillectomy he was admittedwith a localized left-sided empyema from which Actino-myces israeli was grown. The empyema was excised;no abnormality could be felt in the lung itself. He wasgiven a total of 116 mega units of penicillin over 42 daysand also 20 g. terramycin. He was discharged healedfive weeks after the operation.

FIG. E.B. 1

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FIG. E.B.2

CASES SUBJECTED TO LUNG RESECTION.-Theliterature contains few references to the fate ofpatients with actinomycosis who have been sub-jected to lung resection. Kugel and others (1953)report three cases in which lobectomy or pneu-monectomy was performed, all under erroneouspre-operative diagnoses: two patients were thoughtto suffer from bronchial carcinoma and the thirdfrom a chronic lung abscess. All three patientsmade a good recovery, although only one hadpenicillin for a significant period post-operatively.Reitter (1954) described two cases treated bylobectomy, one after prior treatment by chemo-therapy, antibiotics, radiation, and drainage oflung abscess. Both patients recovered. Sevencases in this series were subjected to lung resection:in no case was a correct pre-operative diagnosisof actinomycosis made. Of these the followinghave been selected to illustrate some of the problemsencountered in this group.

W. C., a man of 54 years, gave a history of coughand purulent blood-stained sputum for four months.Tomography demonstrated a cavity in the right upperlobe with thick, irregular walls. A diagnosis of breaking-down neoplasm was made and pneumonectomy carriedout (August, 1948). Histologically the lesion was a

typical actinomycotic abscess. He developed anempyema post-operatively which was treated conserva-tively. He remained well for over five years, but diedsuddenly after developing a bronchopleural fistula.

In the following case a supposed chronic lungabscess provided the indication for surgery.

C. F., a woman of 58 years, had had repeatedhaemoptyses of up to half a pint over a six-year period.A radiograph showed an ill-defined rounded opacityin the anterior segment of the left upper lobe. Broncho-scopy showed pus coming from the left upper lobeorifice and bronchography suggested a chronic lungabscess. At thoracotomy a densely adherent left upperlobe containing a stony, hard mass was removed (May,1952). Her post-operative recovery was uneventful.She received 38 mega units of penicillin in the post-operative period. Histologically the removed lobeshowed typical actinomycotic changes. This womanhas remained free of chest symptoms for four yearssince operation and her chest radiograph shows nosign of disease.

Simulation of a chronic lung abscess providedthe indication for surgery in the following case(the youngest in the series).W. R., a girl of 3j years, had a productive cough

for six months with clubbing of the fingers and slightcyanosis. She was transferred from another hospitalwhere foul pus was aspirated, allegedly from the pleura,and penicillin had also been given parenterally. Shewas transferred as an empyema and on admission wasill and febrile. Bronchoscopy showed evil pus pouringfrom the right lower lobe and bronchography consider-able destruction of the right lower lobe bronchus.After a period of preparation thoracotomy wascarried out in the prone position. As soon as thechest was opened and an attempt made to mobilizethe densely adherent lung, respiratory obstructionnecessitated bronchoscopy at which thick material wasaspirated with difficulty. A middle and lower lobectomywas carried out (May, 1952). Her post-operativerecovery was complicated by a wound infection andby slow expansion of the upper lobe. The child hasremained well since 1952. Histologically this was anactinomycotic lesion with very dense fibrosis and severalabscess cavities. A total of 7i million units of penicillinwas given over 18 days.The following patient presented with repeated

severe haemoptyses.P. K., a youth of 19, suffered from repeated severe

haemoptyses. These appeared to originate from theright middle lobe. An exploratory thoracotomy wascarried out and the middle lobe removed (December,1952). The lobe was bronchiectatic and contained anabscess cavity filled by a rugged calcified mass (Figs.P.K. 1 and 2). Actinomyres israeli was isolated fromboth the calcified material and the bronchi. Thepatient made an uneventful recovery.

RESULTS OF TREATMENTThe results of treatment have been difficult to

assess because so few of these patients have beentreated by a single method. Since 1948 most ofthese cases have been treated with antibiotics,combined when necessary with surgery, and theresults show this method to be superior to all others.

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In assessing the results of treatment we havearbitrarily divided the patients into three groups.Those who did not recieve treatment with eithersulphonamides or penicillin are included in GroupA. Group B comprises those patients who receivedless than a month's continuous sulphonamidetherapy or 8 mega units of penicillin.

In the final group are included all whom weconsider to have had adequate antibiotic therapy,although in many cases this has been less than werecomn- end.

RESULTS OF TREATMENT

Pleuropulnmonary(a) Mainly pleural

A.B..

(b) Mainly pulmonaryA..B..C .. .

Bronchopulmonariy(a) Lung abscess

A..B..

(b) Simulating neoplasmC. .

AlediastinalA..B..C. .

Secondclary Extension from abdomenA ..B ..C ..

Extension from neckB ..C . .

18 cases7 (3 alive, 4 dead)I (died of carcinoma colon)10 (10 alive)

27 cases11 (9 dead, 2 not traced)5 (5 dead)

11 (8 alive, 3 dead)

7 cases3 (I alive, 2 dead)I (dead)3 (3 alive)

5 cases5 (4 alive, I dead)

6 cases3 (3 dead)2 (2 dead)I (alive)

13 cases3 (3 dead)4 (4 dead)6 (4 alive, 2 dead)

2 cases1 (dead)1 (alive)

Metastatic Pyaemia 2 casesC.2 (2 alive)

Chest wall 5 casesA.2 (2 dead)C.3 (3 alive)

Cardiac .. .. No cases

Total cases . 85A.29(4 alive, 23 dead, 2 not

traced)B.14 (14 dead)C.42 (36 alive, 6 dead)

SUMMARY AND CONCLUSIONSThis paper is based on the study of 85 cases of

thoracic actinomycosis.The course of thoracic actinomycosis is traced

from its first clinical description in 1882.Difficulties in treatment, and confusion regarding

the nomenclature of this disease are described,and the name for the causative organism establishedas Actinomyces israeli.The extensive literature on the subject is reviewed,

with particular reference to the various forms oftherapy.

FIG. P.K.I

FIG. P.K.2

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A new classification for thoracic actinomycosisis presented.The various aspects of the aetiology are discussed

stressing the aspiration of infected material fromteeth and tonsils.

Clinical cases are presented illustrating thedifferent varieties in our classification.The epidemiology and pathology are discussed,

and the specific histological reactions produced inthe lungs by Actinomyces israeli are illustrated.The diagnosis is discussed under three main

headings.Penicillin is the most effective therapy, provided

it is given in adequate dosage for a sufficient lengthof time.The results of treatment are given for the 85 cases

in this series.

We should like to thank the following physiciansand surgeons who have kindly allowed us to includetheir cases: Mr. A. L. d'Abreu, Prof. P. Allison,Mr. Hedley Atkins, Mr. R. S. Barclay, Mr. J. R. Belcher,Sir Russell Brock, Prof. R. V. Christie, Mr. W. P.Cleland, Dr. Maurice Davidson, Mr. H. MorristonDavies, Dr. Vernon Davies, Mr. J. Dobson, Mr. A.Eckhoff, Mr. F. Ronald Edwards, Mr. A. W. Fawcett,Mr. G. Flavell, Dr. H. M. Foreman, Dr. A. W. Franklin,Mr. J. S. Glennie, Mr. Kent Harrison, Dr. E. Hayward,Mr. J. P. Hosford, Dr. L. E. Houghton, Dr. J. P. Hur-ford, Mr. J. Jemson, Dr. P. F. Lee Lander, Mr. G. Mason,Dr. J. Maxwell, Dr. F. H. Packer, Mr. C. Parish, Mr.Laurie Pile, Mr. W. H. C. Romanis, Prof. Sir JamesPaterson Ross, Dr. R. Bodley Scott, Mr. T. HolmesSellors, Dr. G. Simon, Mr. Tom Smiley, Dr. K. Taller-man, Mr. Dillwyn Thomas, Sir Clement Price Thomas,Mr. Vernon Thompson, Mr. 0. S. Tubbs, Prof. A. G.Watkins.

Our special thanks are due to Mr. 0. S. Tubbs, whohas given us every possible help and encouragement inthe preparation of this paper.

Professor L. P. Garrod has carried out the bacterio-logical studies on many of the patients in this series.and to him we are particularly grateful.

Dr. J. F. Heggie, of the North Middlesex Hospital,has kindly contributed the section dealing with morbidanatomy and histology.

The colour photomicrographs are the work of Mr. H.Knight, of Chase Farm Hospital.Mr. C. M. Cook, of the Photographic Department of

the Royal Society of Medicine, took the colour photo-graph of the pneumonectomy specimen.We are grateful to the Edmonton Group Hospital

Management Committee, and to Messrs. Glaxo Labora-tories, Ltd., for contributions towards the colourreproductions.

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